2021, Meng, Xia, Liu, Cong, Chen, Renjie, Sera, Francesco, Vicedo-Cabrera, Ana Maria, Milojevic, Ai, Guo, Yuming, Tong, Shilu, Coelho, Micheline de Sousa Zanotti Stagliorio, Saldiva, Paulo Hilario Nascimento, Lavigne, Eric, Correa, Patricia Matus, Ortega, Nicolas Valdes, Osorio, Samuel, Garcia, null, Kyselý, Jan, Urban, Aleš, Orru, Hans, Maasikmets, Marek, Jaakkola, Jouni J. K., Ryti, Niilo, Huber, Veronika, Schneider, Alexandra, Katsouyanni, Klea, Analitis, Antonis, Hashizume, Masahiro, Honda, Yasushi, Ng, Chris Fook Sheng, Nunes, Baltazar, Teixeira, João Paulo, Holobaca, Iulian Horia, Fratianni, Simona, Kim, Ho, Tobias, Aurelio, Íñiguez, Carmen, Forsberg, Bertil, Åström, Christofer, Ragettli, Martina S., Guo, Yue-Liang Leon, Pan, Shih-Chun, Li, Shanshan, Bell, Michelle L., Zanobetti, Antonella, Schwartz, Joel, Wu, Tangchun, Gasparrini, Antonio, Kan, Haidong

Objective To evaluate the short term associations between nitrogen dioxide (NO2) and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide, using a uniform analytical protocol. Design Two stage, time series approach, with overdispersed generalised linear models and multilevel meta-analysis. Setting 398 cities in 22 low to high income countries/regions. Main outcome measures Daily deaths from total (62.8 million), cardiovascular (19.7 million), and respiratory (5.5 million) causes between 1973 and 2018. Results On average, a 10 μg/m3 increase in NO2 concentration on lag 1 day (previous day) was associated with 0.46% (95% confidence interval 0.36% to 0.57%), 0.37% (0.22% to 0.51%), and 0.47% (0.21% to 0.72%) increases in total, cardiovascular, and respiratory mortality, respectively. These associations remained robust after adjusting for co-pollutants (particulate matter with aerodynamic diameter ≤10 μm or ≤2.5 μm (PM10 and PM2.5, respectively), ozone, sulfur dioxide, and carbon monoxide). The pooled concentration-response curves for all three causes were almost linear without discernible thresholds. The proportion of deaths attributable to NO2 concentration above the counterfactual zero level was 1.23% (95% confidence interval 0.96% to 1.51%) across the 398 cities. Conclusions This multilocation study provides key evidence on the independent and linear associations between short term exposure to NO2 and increased risk of total, cardiovascular, and respiratory mortality, suggesting that health benefits would be achieved by tightening the guidelines and regulatory limits of NO2.

2020, Bakalis, Serafim, Valdramidis, Vasilis P., Argyropoulos, Dimitrios, Ahrne, Lilia, Chen, Jianshe, Cullen, P.J., Cummins, Enda, Datta, Ashim K., Emmanouilidis, Christos, Foster, Tim, Fryer, Peter J., Gouseti, Ourania, Hospido, Almudena, Knoerzer, Kai, LeBail, Alain, Marangoni, Alejandro G., Rao, Pingfan, Schlüter, Oliver K., Taoukis, Petros, Xanthakis, Epameinondas, Van Impe, Jan F.M.

[no abstract available]

2020, Waithe, Dominic, Brown, Jill M., Reglinski, Katharina, Diez-Sevilla, Isabel, Roberts, David, Eggeling, Christian

Object detection networks are high-performance algorithms famously applied to the task of identifying and localizing objects in photography images. We demonstrate their application for the classification and localization of cells in fluorescence microscopy by benchmarking four leading object detection algorithms across multiple challenging 2D microscopy datasets. Furthermore we develop and demonstrate an algorithm that can localize and image cells in 3D, in close to real time, at the microscope using widely available and inexpensive hardware. Furthermore, we exploit the fast processing of these networks and develop a simple and effective augmented reality (AR) system for fluorescence microscopy systems using a display screen and back-projection onto the eyepiece. We show that it is possible to achieve very high classification accuracy using datasets with as few as 26 images present. Using our approach, it is possible for relatively nonskilled users to automate detection of cell classes with a variety of appearances and enable new avenues for automation of fluorescence microscopy acquisition pipelines. © 2020 Waithe et al.

2020, Clauder, Franziska, Zitzmann, Franziska D., Friebe, Sabrina, Mayr, Stefan G., Robitzki, Andrea A., Beck-Sickinger, Annette G.

Insufficient endothelialization of cardiovascular devices is a high-risk factor for implant failure. Presentation of extracellular matrix (ECM)-derived coatings is a well-known strategy to improve implant integration. However, the complexity of the system is challenging and strategies for applying multifunctionality are required. Here, we engineered mussel-derived surface-binding peptides equipped with integrin (c[RGDfK]) and proteoglycan binding sites (FHRRIKA) for enhanced endothelialization. Surface-binding properties of the platform containing l-3,4-dihydroxyphenylalanine (DOPA) residues were confirmed for hydrophilized polycaprolactone-co-lactide scaffolds as well as for glass and polystyrene. Further, heparin and the heparin-binding angiogenic factors VEGF, FGF-2 and CXCL12 were immobilized onto the peptide in a modular assembly. Presentation of bioactive peptides greatly enhanced human umbilical vein endothelial cell (HUVEC) adhesion and survival under static and fluidic conditions. In subsequent investigations, peptide-heparin-complexes loaded with CXCL12 or VEGF had an additional increasing effect on cell viability, differentiation and migration. Finally, hemocompatibility of the coatings was ensured. This study demonstrates that coatings combining adhesion peptides, glycosaminoglycans and modulators are a versatile tool to convey ECM-inspired multifunctionality to biomaterials and efficiently promote their integration. © 2020 The Royal Society of Chemistry.

2020, Gorzkiewicz, Michal, Konopka, Malgorzata, Janaszewska, Anna, Tarasenko, Irina I., Sheveleva, Nadezhda N., Gajek, Arkadiusz, Neelov, Igor M., Klajnert-Maculewicz, Barbara

In order to enhance intracellular uptake and accumulation of therapeutic nucleic acids for improved gene therapy methods, numerous delivery vectors have been elaborated. Based on their origin, gene carriers are generally classified as viral or non-viral vectors. Due to their significantly reduced immunogenicity and highly optimized methods of synthesis, nanoparticles (especially those imitating natural biomolecules) constitute a promising alternative for virus-based delivery devices. Thus, we set out to develop innovative peptide dendrimers for clinical application as transfection agents and gene carriers. In the present work we describe the synthesis of two novel lysine-based dendritic macromolecules (D3K2 and D3G2) and their initial characterization for cytotoxicity/genotoxicity and transfection potential in two human cell line models: cervix adenocarcinoma (HeLa) and microvascular endothelial (HMEC-1). This approach allowed us to identify more cationic D3K2 as potent delivery agent, being able to increase intracellular accumulation of large nucleic acid molecules such as plasmids. Moreover, the dendrimers exhibited specific cytotoxicity towards cancer cell line without showing significant toxic effects on normal cells. These observations are promising prognosis for future clinical application of this type of nanoparticles. © 2019 The Authors